DESCRIPTION (provided by investigator): This proposal intends to explore the therapeutic potential of human bone marrow derived multipotent adult stem cells (MAPCs) for neural transplantation and repair. MAPCs could provide a (1) source of grafting tissue for cell replacement therapies and (2) gene therapy vehicles to correct metabolic or neurochemical deficiencies in the CNS. We will test whether human MAPCs can migrate and undergo neuronal, site-specific differentiation in vivo by transplanting them into neonatal rats. Since cholinergic basal forebrain degeneration is correlated with cognitive decline in Alzheimer?s disease, we will particularly addresss the potential for cholinergic differentiation of MAPCs when transplanted in this region. Ex-vivo nerve growth factor gene transfer has been shown to be a suitable approach to improve the cognitive deficits associated with degeneration of the basal forebrain cholinergic system, as seen in aging and Alzheimer?s disease. As gene therapy vehicles, we are interested in determining the effectiveness of NGF-secreting MAPCs transplants to ameliorate the cognitive deficits of animals with partial cholinergic immunolesions. Therefore, our experiments will test the role for MAPCs as a readily available source for neural transplantation tissue that besides the advantage of being amenable to expansion, differentiation and genetic manipulation in vitro, also embodies the unique prospect for autologous transplantation.